Key Laboratory of Biopesticide and Chemical Biology (Ministry of Education), College of Plant Protection, Fujian Agriculture and Forestry University, Fuzhou, Fujian, China.
Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Guangdong Public Laboratory of Wild Animal Conservation and Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, Guangdong 510260, China.
Biomed Pharmacother. 2023 Oct;166:115412. doi: 10.1016/j.biopha.2023.115412. Epub 2023 Sep 4.
Acute lung injury (ALI) is an inflammation-mediated respiratory disease with a high mortality rate. Medications with anti-inflammatory small molecules have been demonstrated in phase I and II clinical trials to considerably reduce the ALI mortality. In this study, two series of lansiumamide analogues were designed, synthesized, and evaluated for anti-inflammatory activity for ALI treatment. We found that compound 8n exhibited the best anti-inflammatory activity through inhibiting LPS-induced expression of the proinflammatory cytokines interleukin-6 (IL-6) and interleukin-1β (IL-1β) in Raw264.7 cells and activating the Nrf2/HO-1 pathway. Furthermore, we discovered in a LPS-induced ALI mice model that compound 8n significantly reduced the infiltration of inflammatory cells into lung tissue to achieve the effect of protecting lung tissues and improving ALI. Additionally, our mice model study revealed that compound 8n had a good expectorant effect. These results consistently support that lansiumamide analogue 8n represents a new class of anti-inflammatory agents with potential as a lead compound for further development into a therapeutic drug for ALI treatment.
急性肺损伤（ALI）是一种炎症介导的呼吸系统疾病，死亡率很高。在 I 期和 II 期临床试验中，具有抗炎作用的小分子药物已被证明能显著降低 ALI 的死亡率。在这项研究中，设计、合成了两系列 Lansiumamide 类似物，并对其用于治疗 ALI 的抗炎活性进行了评估。我们发现，化合物 8n 通过抑制 LPS 诱导的 Raw264.7 细胞中促炎细胞因子白细胞介素-6（IL-6）和白细胞介素-1β（IL-1β）的表达以及激活 Nrf2/HO-1 通路，表现出最佳的抗炎活性。此外，我们在 LPS 诱导的 ALI 小鼠模型中发现，化合物 8n 能显著减少炎症细胞浸润肺组织，从而达到保护肺组织和改善 ALI 的效果。此外，我们的小鼠模型研究表明，化合物 8n 具有良好的祛痰作用。这些结果一致表明， Lansiumamide 类似物 8n 代表了一类新的抗炎药物，有可能成为进一步开发治疗 ALI 药物的先导化合物。
